Collateral effects of drug resistance evolution: explaining repeatability and directionality patterns

Clonal interference can explain unidirectional cross-resistance and increase repeatability, while strong selection with weak mutation increases non-repeatability in drug-resistance evolution models.

• Why it matters: Collateral sensitivity and cross-resistance are not consistently repeatable or bidirectional, limiting clinical use and making it unclear which evolutionary regimes and genetics produce reliable patterns.
• What they did: The study builds minimal examples using the fewest loci and conditions to generate repeatable versus non-repeatable and uni- versus bidirectional collateral effects, varying drug concentration, population dynamics, and genetic architecture.
• The result: Drug dose can shift the collateral effect and its pattern, and the selection regime (drug dose and population dynamics) is linked to non-repeatability and unidirectionality, guiding future modeling plus mutation and full dose-response measurements.

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